Abstract 3321: Immunogenic clearance sensitizes cold tumor to PD-1 blockade by enhancing quantity and quality of CD8+ T cells

Abstract

Abstract The effective immune response against cancer requires stepwise events from the release of tumor antigens to T cells' exhibiting cytotoxic effects in the tumor microenvironment (TME). Immunogenic clearance reveals intrinsic tumor antigenicity with immunogenic cell death of the tumor cells and increases priming of T cells with increased phagocytosis activity of professional antigen-presenting cells (pAPCs), therefore, overcome the failure in immune surveillance of cancer caused by immunological ignorance. Here, we investigated the potential strategy to induce immunogenic clearance with immunogenic cell death (ICD) inducers and phagocytosis enhancer. Using anthracyclines, one of the renowned ICD inducers and fasudil, rho-kinase (ROCK) inhibitors that increases phagocytosis activity, reinforced cross-presentation of dendritic cells and cross-priming of CD8+ T cells in secondary lymphoid organ contributes to consecutive infiltration of CD8+ T cells in TME. Inducing the CD8+ T cell immune response, this strategy could surmount the resistance to immune checkpoint blockade of the immunologically cold tumor where little infiltrated T cells exist in the tumor site, which leads not just increased tumor-specific CD8+ T cells, but prolonged survival accompanied with the formation of sustainable CD8+ T cell memory. Citation Format: Gi-Hoon Nam, Yoonjeong Choi, In-San Kim. Immunogenic clearance sensitizes cold tumor to PD-1 blockade by enhancing quantity and quality of CD8+ T cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3321.